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1.
HIV Med ; 24(7): 838-844, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36895097

RESUMO

OBJECTIVE: Our objectives were to investigate the recent frequency of cerebrospinal fluid (CSF) HIV RNA escape and other CSF viral nucleic acid detection in people with HIV with neurological symptoms and to assess associated clinical factors. METHOD: This was a retrospective cohort analysis of people with HIV who underwent CSF examination for clinical indications between 2017 and 2022. Individuals were identified from pathology records, and clinical data were recorded. CSF HIV RNA escape was defined as CSF HIV RNA concentrations greater than in plasma. CSF viral screen included herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV), Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and JC virus. When cases were detected in five or more people with HIV, associated clinical factors were assessed using linear regression modelling. RESULTS: CSF HIV RNA escape was observed in 19 of 114 individuals (17%) and was associated with the presence of HIV drug resistance mutations and non-integrase strand transfer inhibitor-based antiretroviral therapy (p < 0.05 for all) when compared to people with HIV without escape. Positive viral nucleic acid testing included EBV (n = 10), VZV (3), CMV (2), HHV-6 (2) and JC virus (4). Detectable CSF EBV was not considered related to neurological symptoms and was associated with concomitant CSF infections in eight of ten individuals and with CSF pleocytosis, previous AIDS, lower nadir and current CD4 T-cell count (p < 0.05 for all). CONCLUSION: In people with HIV with neurological symptoms, the frequency of CSF HIV RNA escape remains similar to that in historical reports. Detectable EBV viral nucleic acid in the CSF was observed frequently and, in the absence of clinical manifestations, may be a consequence of CSF pleocytosis.


Assuntos
Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Infecções por HIV , Infecções por Herpesviridae , Humanos , Infecções por Herpesviridae/líquido cefalorraquidiano , Infecções por Herpesviridae/diagnóstico , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Estudos Retrospectivos , Leucocitose/complicações , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Herpesvirus Humano 3/genética , Citomegalovirus , RNA , Líquido Cefalorraquidiano , DNA Viral
2.
Clin Infect Dis ; 72(1): 82-89, 2021 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-32634822

RESUMO

BACKGROUND: Understanding nosocomial acquisition, outbreaks, and transmission chains in real time will be fundamental to ensuring infection-prevention measures are effective in controlling coronavirus disease 2019 (COVID-19) in healthcare. We report the design and implementation of a hospital-onset COVID-19 infection (HOCI) surveillance system for an acute healthcare setting to target prevention interventions. METHODS: The study took place in a large teaching hospital group in London, United Kingdom. All patients tested for SARS-CoV-2 between 4 March and 14 April 2020 were included. Utilizing data routinely collected through electronic healthcare systems we developed a novel surveillance system for determining and reporting HOCI incidence and providing real-time network analysis. We provided daily reports on incidence and trends over time to support HOCI investigation and generated geotemporal reports using network analysis to interrogate admission pathways for common epidemiological links to infer transmission chains. By working with stakeholders the reports were co-designed for end users. RESULTS: Real-time surveillance reports revealed changing rates of HOCI throughout the course of the COVID-19 epidemic, key wards fueling probable transmission events, HOCIs overrepresented in particular specialties managing high-risk patients, the importance of integrating analysis of individual prior pathways, and the value of co-design in producing data visualization. Our surveillance system can effectively support national surveillance. CONCLUSIONS: Through early analysis of the novel surveillance system we have provided a description of HOCI rates and trends over time using real-time shifting denominator data. We demonstrate the importance of including the analysis of patient pathways and networks in characterizing risk of transmission and targeting infection-control interventions.


Assuntos
COVID-19 , Hospitais , Humanos , Londres , SARS-CoV-2 , Reino Unido
3.
J Synchrotron Radiat ; 28(Pt 3): 961-969, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33950004

RESUMO

A new diffraction beamline for materials science has been built at the Canadian Light Source synchrotron. The X-ray source is an in-vacuum wiggler with a 2.5 T peak magnetic field at 5.2 mm gap. The optical configuration includes a toroidal mirror, a single side-bounce Bragg monochromator, and a cylindrical mirror, producing a sub-150 µm vertical × 500 µm horizontal focused beam with a photon energy range of 7-22 keV and a flux of 1012 photons per second at the sample position. Three endstations are currently open to general users, and the techniques available include high-resolution powder diffraction, small molecule crystallography, X-ray reflectivity, in situ rapid thermal annealing, and SAXS/WAXS. The beamline design parameters, calculated and measured performance, and initial experimental results are presented to demonstrate the capabilities for materials science.

5.
Physiol Plant ; 162(3): 316-332, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28857201

RESUMO

Wheat (Triticum aestivum L.) is the largest cereal crop grown in Western Canada where drought during late vegetative and seed filling stages affects plant development and yield. To identify new physiochemical markers associated with drought tolerance, epidermal characteristics of the flag leaf of two wheat cultivars with contrasting drought tolerance were investigated. The drought resistant 'Stettler' had a lower drought susceptibility index, greater harvest index and water-use efficiency than the susceptible 'Superb'. Furthermore, flag leaf width, relative water content and leaf roll were significantly greater in Stettler than in Superb at moderate drought stress (MdS). Visible differences in epicuticular wax density on the adaxial flag leaf surfaces and larger bulliform cells were identified in Stettler as opposed to Superb. Mid-infrared attenuated total internal reflectance spectra revealed that Stettler flag leaves had increased asymmetric and symmetric CH2 but reduced carbonyl esters on its adaxial leaf surface compared to Superb under MdS. X-ray fluorescence spectra revealed a significant increase in total flag leaf Zn concentrations in Stettler in response to MdS. Such information on the microstructural and chemical features of flag leaf may have potential as markers for drought tolerance and thereby accelerate the selection and release of more drought-resistant cultivars.


Assuntos
Secas , Folhas de Planta/metabolismo , Triticum/metabolismo , Ceras/metabolismo , Adaptação Fisiológica , Microscopia Eletrônica de Varredura , Folhas de Planta/anatomia & histologia , Folhas de Planta/ultraestrutura , Especificidade da Espécie , Espectroscopia de Infravermelho com Transformada de Fourier , Estresse Fisiológico , Síncrotrons , Triticum/anatomia & histologia , Triticum/classificação , Água/metabolismo , Ceras/química , Espectroscopia por Absorção de Raios X
6.
Lab Invest ; 96(10): 1105-15, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27617404

RESUMO

Neurofibromas, which are benign Schwann cell tumors, are the hallmark feature in the autosomal dominant condition neurofibromatosis 1 (NF1) and are associated with biallelic loss of NF1 gene function. There is a need for effective therapies for neurofibromas, particularly the larger, plexiform neurofibromas. Tissue culture is an important tool for research. However, it is difficult to derive enriched human Schwann cell cultures, and most enter replicative senescence after 6-10 passages, impeding cell-based research in NF1. Through exogenous expression of human telomerase reverse transcriptase and murine cyclin-dependent kinase (mCdk4), normal (NF1 wild-type), neurofibroma-derived Schwann cells heterozygous for NF1 mutation, and neurofibroma-derived Schwann cells homozygous for NF1 mutation were immortalized, including some matched samples from the same NF1 patient. Initial experiments employed retroviral vectors, while subsequent work utilized lentiviral vectors carrying these genes because of improved efficiency. Expression of both transgenes was required for immortalization. Molecular and immunohistochemical analysis indicated that these cell lines are of Schwann cell lineage and have a range of phenotypes, many of which are consistent with their primary cultures. This is the first report of immortalization and detailed characterization of multiple human NF1 normal nerve and neurofibroma-derived Schwann cell lines, which will be highly useful research tools to study NF1 and other Schwann tumor biology and conditions.


Assuntos
Técnicas de Cultura de Células , Neurofibromatose 1 , Células de Schwann , Animais , Linhagem Celular Tumoral , Quinase 4 Dependente de Ciclina/genética , Humanos , Camundongos , Transplante de Neoplasias , Telomerase/genética
7.
Hum Mol Genet ; 21(2): 322-33, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-21989056

RESUMO

The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in the region, in two independent monocyte gene expression data sets. Critically, using chromosome conformation capture (3C), we identified physical proximity between the DEXI promoter region and intron 19 of CLEC16A, separated by a loop of >150 kb. In reciprocal experiments, a 20 kb fragment of intron 19 of CLEC16A, containing SNPs associated with T1D and MS, as well as with DEXI expression, interacted with the promotor region of DEXI but not with candidate DNA fragments containing other potential causal genes in the region, including CLEC16A. Intron 19 of CLEC16A is highly enriched for transcription-factor-binding events and markers associated with enhancer activity. Taken together, these data indicate that although the causal variants in the 16p13 region lie within CLEC16A, DEXI is an unappreciated autoimmune disease candidate gene, and illustrate the power of the 3C approach in progressing from genome-wide association studies results to candidate causal genes.


Assuntos
Doenças Autoimunes/genética , Proteínas de Ligação a DNA/genética , DNA/genética , Proteínas de Membrana/genética , Cromossomos Humanos Par 16 , Humanos , Monócitos/metabolismo , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
8.
J Med Virol ; 86(2): 235-40, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24166559

RESUMO

A woman developed acute hepatitis C (HCV) infection 2 months after delivering her baby at a London Hospital. The other patients who had been on the unit at the same time all had negative HCV serology antenatally. Testing of the healthcare workers who had been involved in this patient's care revealed that one of the midwives who only worked on the postnatal unit was chronically infected with the same viral genotype. Sequencing and phylogenetic analysis revealed close identity between the viruses from the two individuals. Although, the midwife had only performed non-exposure prone procedures including venepuncture and cannulation, our findings indicate that transmission of the virus had occurred from the healthcare worker to the patient. The potential implications of this case within the setting of national policy on blood borne viruses and healthcare workers are discussed.


Assuntos
Hepacivirus/classificação , Hepacivirus/isolamento & purificação , Hepatite C/transmissão , Adulto , Análise por Conglomerados , Transmissão de Doença Infecciosa , Feminino , Genótipo , Pessoal de Saúde , Hepacivirus/genética , Hepatite C/virologia , Hospitais , Humanos , Londres , Tocologia , Epidemiologia Molecular , Dados de Sequência Molecular , Filogenia , RNA Viral/genética , Análise de Sequência de DNA
9.
BMJ Case Rep ; 17(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38960425

RESUMO

A woman in her 40s known to have systemic lupus erythematosus presented with a maculopapular rash on her face, neck and chest following measles exposure. She had received a single-dose measles vaccine as a child in the 1970s and was therefore presumed to be immune, and thus not infectious. As a result, she was initially managed in an open bay. Measles virus IgM antibody in serum was undetectable; however, measles virus RNA was subsequently detected in throat swab by PCR, which is consistent with current infection. Measles is one of the most transmissible diseases in the world and cases are rising both in the UK and globally. Our case and literature review highlight the risk of vaccine failure in measles, especially in people who have not received two doses of the measles, mumps and rubella vaccine. It also highlights the challenges in diagnosing measles in previously vaccinated individuals.


Assuntos
Sarampo , Humanos , Sarampo/prevenção & controle , Sarampo/diagnóstico , Feminino , Vacina contra Sarampo , Adulto , Vírus do Sarampo/imunologia , Vírus do Sarampo/isolamento & purificação , Vacina contra Sarampo-Caxumba-Rubéola , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Vacinação , Pessoa de Meia-Idade , Anticorpos Antivirais/sangue , Imunoglobulina M/sangue
10.
Audiol Res ; 14(4): 649-658, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39051199

RESUMO

BACKGROUND: Cochlear implantation (CI) has proven to be a highly effective method for rehabilitating individuals with severe to profound hearing loss. However, challenges persist, particularly in cases where CI failure necessitates re-implantation. This study aims to address the gap in understanding the knowledge and practices of audiologists in the UK regarding cochlear re-implantation through a comprehensive questionnaire survey. METHODS: A bespoke questionnaire was distributed to audiologists working with CI across the UK. The survey, which included multiple-choice items, open-text responses, and visual analogue scales, was made accessible via an online link shared through professional bodies, email groups, and social media platforms. RESULTS: The survey received 27 responses, predominantly from female audiologists (71.4%), with significant representation from London (28.6%) and the East of England (21.4%). A majority of respondents had over 16 years of CI experience (35.7%) and held a master's degree (60.7%). Key reasons for CI re-implantation included electrode failure (82.1%) and hermetic seal failure (60.7%). While respondents showed strong confidence in counselling (88.8%) and managing re-implanted devices (84.6%), there was a noted variation in opinions regarding the need for additional training in intraoperative measures. CONCLUSION: This survey highlights the current practices and training needs of UK audiologists in CI re-implantation. This underscores the importance of targeted training to fill knowledge gaps and improve clinical care during CI re-implantation, ultimately enhancing outcomes for both audiologists and CI recipients.

11.
J Synchrotron Radiat ; 20(Pt 2): 272-85, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23412484

RESUMO

The efficiency of soft X-ray diffraction gratings is studied using measurements and calculations based on the differential method with the S-matrix propagation algorithm. New open-source software is introduced for efficiency modelling that accounts for arbitrary groove profiles, such as those based on atomic force microscopy (AFM) measurements; the software also exploits multi-core processors and high-performance computing resources for faster calculations. Insights from these calculations, including a new principle of optimal incidence angle, are used to design a soft X-ray emission spectrometer with high efficiency and high resolution for the REIXS beamline at the Canadian Light Source: a theoretical grating efficiency above 10% and resolving power E/ΔE > 2500 over the energy range from 100 eV to 1000 eV are achieved. The design also exploits an efficiency peak in the third diffraction order to provide a high-resolution mode offering E/ΔE > 14000 at 280 eV, and E/ΔE > 10000 at 710 eV, with theoretical grating efficiencies from 2% to 5%. The manufactured gratings are characterized using AFM measurements of the grooves and diffractometer measurements of the efficiency as a function of wavelength. The measured and theoretical efficiency spectra are compared, and the discrepancies are explained by accounting for real-world effects: groove geometry errors, oxidation and surface roughness. A curve-fitting process is used to invert the calculations to predict grating parameters that match the calculated and measured efficiency spectra; the predicted blaze angles are found to agree closely with the AFM estimates, and a method of characterizing grating parameters that are difficult or impossible to measure directly is suggested.

12.
Sex Transm Infect ; 89(5): 398-403, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23430706

RESUMO

OBJECTIVES: To investigate what factors influence the detection of Chlamydia trachomatis antibody following genital tract infection. METHODS: One hundred and sixty-four women with a previous history of C trachomatis infection contributed to an earlier report on the performance of chlamydia antibody ELISA assays. We undertook further analysis to explore how chlamydia antibody assay sensitivity changes with time since infection. RESULTS: Chlamydia antibody was detected in more women soon after the last detection of chlamydia at the lower genital tract than at later times. This holds true for all tests, but the Anilabsystems IgG EIA, Medac pELISA plus ELISA and the Savyon SeroCT-IgG ELISA were less sensitive than the pgp3 ELISA and the Anilabsystems microimmunofluorescence (MIF) assay at all time points except during current infection. Fall in seropositivity in women generally occurred in the early weeks and months following the last episode of chlamydia infection. There was no clear pattern of further reduction in seropositivity after 6 months. Multiple previous episodes were associated with increased seropositivity in the pgp3 assay (two or more vs one, OR 19, p<0.001) and other tests, but the effect was significantly smaller for the Anilabs, Medac and SeroCT MOMP peptide ELISAs, but not for the MIF assay. CONCLUSIONS: Chlamydia antibody detection decreases with time since infection and this is most apparent in the first 6 months. In women who have had more than one infection, antibody remained detectable longer for all tests, but this was more marked for the pgp3 ELISA and MIF assay.


Assuntos
Infecções por Chlamydia/imunologia , Chlamydia trachomatis/isolamento & purificação , Adulto , Anticorpos Antibacterianos , Infecções por Chlamydia/epidemiologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Valor Preditivo dos Testes , Comportamento Sexual , Fatores de Tempo , Reino Unido/epidemiologia
13.
Heliyon ; 9(11): e22139, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38045167

RESUMO

Synchrotron X-ray imaging and spectroscopy techniques were used for studying changes during post-harvest storage of food grains. Three varieties (AAC Spitfire, CDC Defy, and AAC Stronghold) of the Canada Western Amber Durum (CWAD) wheat class were stored for five weeks at 17 % moisture content (wb). Control (dry) and stored moistened seeds were analyzed for biochemical and nutritional changes using synchrotron bulk X-ray fluorescence spectroscopy (SR-XRF), X-ray fluorescence imaging (SR-XFI), and mid-infrared (mid-IR) spectroscopy at the Canadian Light Source (CLS), Saskatoon, SK. All varieties of durum wheat were spoiled at the end of five week, and AAC Spitfire and CDC Defy varieties were most affected in nutritional composition and their distribution than AAC Stronghold. Variable response to changes in biochemical and nutrition were found in all three spoiled varieties of the same durum wheat class.

14.
Int J Infect Dis ; 126: 48-53, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36410691

RESUMO

OBJECTIVES: Since May 2022, cases of human monkeypox virus (hMPXV) with human-to-human cross-transmission have significantly increased in nonendemic countries. Our aim was to characterize diagnostic features of patients with confirmed and possible monkeypox to guide future risk stratification and to describe a virtual care model. METHODS: We performed a retrospective case-control study of 140 patients assessed and screened for suspected monkeypox; on hMPXV polymerase chain reaction testing, 70 were confirmed positive, and 70 were negative. Data were compared to generate odds ratios of demographic and clinical features. RESULTS: Patients who tested positive were predominantly cis-male (99%) and self-identified as gay, bisexual, and other men who have sex with men (94%). Lymphadenopathy at presentation was associated with a higher likelihood of a positive result (odds ratio [OR] 7.69 [95% confidence interval (CI) 3.58, 16.51]). Patients who tested positive were more likely to have a rash affecting the genital (OR 5.38 [95% CI 2.57, 11.23]) or buttocks/perianal region (OR 3.79 [1.70, 8.45]) than negative controls. A total of 79% of patients were engaged with a virtual ward follow-up. CONCLUSION: These data can inform a risk-based approach to the management of suspected monkeypox in gay, bisexual, and other men who have sex with men populations. Lymphadenopathy at presentation and the location of the rash were more associated with a positive hMPXV result. Health authorities can consider a virtual ward approach in the hMPHXV outbreak.


Assuntos
Exantema , Linfadenopatia , Mpox , Minorias Sexuais e de Gênero , Humanos , Masculino , Estudos de Casos e Controles , Estudos Retrospectivos , Mpox/diagnóstico , Mpox/epidemiologia , Homossexualidade Masculina , Londres
15.
Open Forum Infect Dis ; 10(5): ofad108, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37152187

RESUMO

Background: We report outcomes and novel characterization of a unique cohort of 42 individuals with persistently indeterminate human immunodeficiency virus (HIV) status, the majority of whom are HIV viral controllers. Methods: Eligible individuals had indeterminate or positive HIV serology, but persistently undetectable HIV ribonucleic acid (RNA) by commercial assays and were not taking antiretroviral therapy (ART). Routine investigations included HIV Western blot, HIV viral load, qualitative HIV-1 deoxyribonucleic acid (DNA), coinfection screen, and T-cell quantification. Research assays included T-cell activation, ART measurement, single-copy assays detecting HIV-1 RNA and DNA, and plasma cytokine quantification. Human immunodeficiency virus seropositivity was defined as ≥3 bands on Western blot; molecular positivity was defined as detection of HIV RNA or DNA. Results: Human immunodeficiency virus infection was excluded in 10 of 42 referrals, remained unconfirmed in 2 of 42, and was confirmed in 30 of 42, who were identified as HIV elite controllers (ECs), normal CD4 T-cell counts (median 820/mL, range 805-1336), and normal CD4/CD8 ratio (median 1.8, range 1.2-1.9). Elite controllers had a median duration of elite control of 6 years (interquartile range = 4-14). Antiretroviral therapy was undetected in all 23 subjects tested. Two distinct categories of ECs were identified: molecular positive (n = 20) and molecular negative (n = 10). Conclusions: Human immunodeficiency virus status was resolved for 95% of referrals with the majority diagnosed as EC. The clinical significance of the 2 molecular categories among ECs requires further investigation.

16.
Lancet Infect Dis ; 23(6): e218-e226, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36773621

RESUMO

A 48-year-old man with poorly controlled HIV presented with severe human monkeypox virus (hMPXV) infection, having completed 2 weeks of tecovirimat at another hospital. He had painful, ulcerating skin lesions on most of his body and oropharyngeal cavity, with subsequent Ludwig's angina requiring repeated surgical interventions. Despite commencing a second, prolonged course of tecovirimat, he did not objectively improve, and new lesions were still noted at day 24. Discussion at the UK National Health Service England High Consequence Infectious Diseases Network recommended the use of 3% topical and then intravenous cidofovir, which was given at 5 mg/kg; the patient made a noticeable improvement after the first intravenous dose. He received further intravenous doses at 7 days and 21 days after the dose and was discharged at day 52. Cidofovir is not licensed for use in treatment of hMPXV infection. Data for cidofovir use in hMPXV are restricted to studies in animals. Four other documented cases of cidofovir use against hMPXV have been reported in the USA in 2022, but we present its first use in the UK. The scarcity of studies into the use of cidofovir in this condition clearly shows the need for robust studies to assess efficacy, optimum dosage, timing, and route of administration.


Assuntos
Infecções por HIV , Mpox , Organofosfonatos , Masculino , Humanos , Pessoa de Meia-Idade , Cidofovir/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Organofosfonatos/uso terapêutico , Mpox/tratamento farmacológico , Medicina Estatal , Citosina/uso terapêutico , Antivirais/uso terapêutico
17.
Appl Environ Microbiol ; 77(17): 5888-96, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21742912

RESUMO

Lake St. Lucia, iSimangaliso Wetland Park, South Africa, is the largest estuarine lake in Africa. Extensive use and manipulation of the rivers flowing into it have reduced freshwater inflow, and the lake has also been subject to a drought of 10 years. For much of this time, the estuary has been closed to the Indian Ocean, and salinities have progressively risen throughout the system, impacting the biotic components of the ecosystem, reducing zooplankton and macrobenthic biomass and diversity in particular. In June 2009, a bloom of a red/orange planktonic microorganism was noted throughout the upper reaches of Lake St. Lucia. The bloom persisted for at least 18 months, making it the longest such bloom on record. The causative organism was characterized by light and electron microscopy and by 16S rRNA sequencing and was shown to be a large, unicellular cyanobacterium most strongly associated with the genus Cyanothece. The extent and persistence of the bloom appears to be unique to Lake St. Lucia, and it is suggested that the organism's resistance to high temperatures, to intense insolation, and to hypersalinity as well as the absence of grazing pressure by salinity-sensitive zooplankton all contributed to its persistence as a bloom organism until a freshwater influx, due to exceptionally heavy summer rains in 2011, reduced the salinity for a sufficient length of time to produce a crash in the cyanobacterium population as a complex, low-salinity biota redeveloped.


Assuntos
Cyanothece/classificação , Cyanothece/crescimento & desenvolvimento , Fitoplâncton/classificação , Fitoplâncton/crescimento & desenvolvimento , Microbiologia da Água , Análise por Conglomerados , Cyanothece/citologia , Cyanothece/genética , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Dados de Sequência Molecular , Filogenia , Fitoplâncton/citologia , Fitoplâncton/genética , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , África do Sul , Áreas Alagadas
18.
Cancer Sci ; 101(9): 1997-2004, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20550523

RESUMO

MicroRNAs (miRNAs) are frequently deregulated in human tumors, and play important roles in tumor development and progression. The pathological roles of miRNAs in neurofibromatosis type 1 (NF1) tumorigenesis are largely unknown. We demonstrated that miR-10b was up-regulated in primary Schwann cells isolated from NF1 neurofibromas and in cell lines and tumor tissues from malignant peripheral nerve sheath tumors (MPNSTs). Intriguingly, a significantly high level of miR-10b correlated with low neurofibromin expression was found in a neuroectodermal cell line: Ewing's sarcoma SK-ES-1 cells. Antisense inhibiting miR-10b in NF1 MPNST cells reduced cell proliferation, migration and invasion. Furthermore, we showed that NF1 mRNA was the target for miR-10b. Overexpression of miR-10b in 293T cells suppressed neurofibromin expression and activated RAS signaling. Antisense inhibition of miR-10b restored neurofibromin expression in SK-ES-1 cells, and decreased RAS signaling independent of neurofibromin in NF1 MPNST cells. These results suggest that miR-10b may play an important role in NF1 tumorigenesis through targeting neurofibromin and RAS signaling.


Assuntos
MicroRNAs/genética , Neurofibromatose 1/genética , Transdução de Sinais , Proteínas ras/genética , Regiões 3' não Traduzidas/genética , Western Blotting , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Neurofibromatose 1/metabolismo , Neurofibromatose 1/patologia , Neurofibromina 1/genética , Neurofibromina 1/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Fosforilação , RNA Antissenso/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células de Schwann/metabolismo , Células de Schwann/patologia , Células Tumorais Cultivadas , Proteínas ras/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-32457227

RESUMO

OBJECTIVE: To describe a novel case of coronavirus disease 2019 (COVID-19)-associated acute necrotizing encephalopathy (ANE) in a patient with aplastic anemia where there was early brain stem-predominant involvement. METHODS: Evaluation of cause, clinical symptoms, and treatment response. RESULTS: A 59-year-old woman with a background of transfusion-dependent aplastic anemia presented with seizures and reduced level of consciousness 10 days after the onset of subjective fever, cough, and headache. Nasopharyngeal swab testing for severe acute respiratory syndrome coronavirus (SARS-CoV-2) was positive, and CT during admission demonstrated diffuse swelling of the brain stem. She required intubation and mechanical ventilation for airway protection, given her reduced level of consciousness. The patient's condition deteriorated, and MRI on day 6 demonstrated worsening brain stem swelling with symmetrical hemorrhagic lesions in the brain stem, amygdalae, putamina, and thalamic nuclei. Appearances were consistent with hemorrhagic ANE with early brain stem involvement. The patient showed no response to steroid therapy and died on the eighth day of admission. CONCLUSIONS: COVID-19 may be associated with an acute severe encephalopathy and, in this case, was considered most likely to represent an immune-mediated phenomenon. As the pandemic continues, we anticipate that the spectrum of neurologic presentation will broaden. It will be important to delineate the full clinical range of emergent COVID-19-related neurologic disease.


Assuntos
Anemia Aplástica/complicações , Infecções por Coronavirus/complicações , Leucoencefalite Hemorrágica Aguda/etiologia , Pneumonia Viral/complicações , Tonsila do Cerebelo/diagnóstico por imagem , Anemia Aplástica/terapia , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Edema Encefálico/fisiopatologia , Edema Encefálico/terapia , Tronco Encefálico/diagnóstico por imagem , COVID-19 , Infecções por Coronavirus/terapia , Dexametasona/uso terapêutico , Imagem de Difusão por Ressonância Magnética , Evolução Fatal , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/fisiopatologia , Leucoencefalite Hemorrágica Aguda/diagnóstico por imagem , Leucoencefalite Hemorrágica Aguda/fisiopatologia , Leucoencefalite Hemorrágica Aguda/terapia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Pandemias , Transfusão de Plaquetas , Pneumonia Viral/terapia , Hemorragia Putaminal/diagnóstico por imagem , Hemorragia Putaminal/etiologia , Hemorragia Putaminal/fisiopatologia , Respiração Artificial , Convulsões/etiologia , Núcleos Talâmicos/diagnóstico por imagem , Tomografia Computadorizada por Raios X
20.
Lancet Microbe ; 1(7): e300-e307, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32964211

RESUMO

BACKGROUND: Access to rapid diagnosis is key to the control and management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory RT-PCR testing is the current standard of care but usually requires a centralised laboratory and significant infrastructure. We describe our diagnostic accuracy assessment of a novel, rapid point-of-care real time RT-PCR CovidNudge test, which requires no laboratory handling or sample pre-processing. METHODS: Between April and May, 2020, we obtained two nasopharyngeal swab samples from individuals in three hospitals in London and Oxford (UK). Samples were collected from three groups: self-referred health-care workers with suspected COVID-19; patients attending emergency departments with suspected COVID-19; and hospital inpatient admissions with or without suspected COVID-19. For the CovidNudge test, nasopharyngeal swabs were inserted directly into a cartridge which contains all reagents and components required for RT-PCR reactions, including multiple technical replicates of seven SARS-CoV-2 gene targets (rdrp1, rdrp2, e-gene, n-gene, n1, n2 and n3) and human ribonuclease P (RNaseP) as sample adequacy control. Swab samples were tested in parallel using the CovidNudge platform, and with standard laboratory RT-PCR using swabs in viral transport medium for processing in a central laboratory. The primary analysis was to compare the sensitivity and specificity of the point-of-care CovidNudge test with laboratory-based testing. FINDINGS: We obtained 386 paired samples: 280 (73%) from self-referred health-care workers, 15 (4%) from patients in the emergency department, and 91 (23%) hospital inpatient admissions. Of the 386 paired samples, 67 tested positive on the CovidNudge point-of-care platform and 71 with standard laboratory RT-PCR. The overall sensitivity of the point-of-care test compared with laboratory-based testing was 94% (95% CI 86-98) with an overall specificity of 100% (99-100). The sensitivity of the test varied by group (self-referred healthcare workers 94% [95% CI 85-98]; patients in the emergency department 100% [48-100]; and hospital inpatient admissions 100% [29-100]). Specificity was consistent between groups (self-referred health-care workers 100% [95% CI 98-100]; patients in the emergency department 100% [69-100]; and hospital inpatient admissions 100% [96-100]). Point of care testing performance was similar during a period of high background prevalence of laboratory positive tests (25% [95% 20-31] in April, 2020) and low prevalence (3% [95% 1-9] in inpatient screening). Amplification of viral nucleocapsid (n1, n2, and n3) and envelope protein gene (e-gene) were most sensitive for detection of spiked SARS-CoV-2 RNA. INTERPRETATION: The CovidNudge platform was a sensitive, specific, and rapid point of care test for the presence of SARS-CoV-2 without laboratory handling or sample pre-processing. The device, which has been implemented in UK hospitals since May, 2020, could enable rapid decisions for clinical care and testing programmes. FUNDING: National Institute of Health Research (NIHR) Imperial Biomedical Research Centre, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England, NIHR Biomedical Research Centre Oxford, and DnaNudge.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Humanos , Testes Imediatos , RNA Viral/genética , Sensibilidade e Especificidade
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